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[A. Biochemistry/Molecular Biology] A-39
Inotodiol Protect Human Dermal Fibroblast Against Oxidative
Stress-induced Aging by Regulating NADPH oxidase 5 and
Erk1/2
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Seung Hoon Lee¹ , Gun-Woo Won¹ , Seung-Hyeon Choi¹, Mi-Yoon Kim¹, Cheong-Hae Oh¹,
Jong-Tae Park²,³*, Jong-Il Park¹*
¹Department of Biochemistry, Research Institute for Medical Science, Chungnam National University School of
Medicine, Daejeon 35015, Korea, ²Department of Food Science and Technolo, Chungnam National University,
Daejeon 35015, Korea, ³CARBOEXPERT Inc, Chungnam National University, Daejeon 34134, Korea
Oxidative damage is one of the major causes of human skin aging. Inotodiol is a lanostane triterpenoid that
demonstrates antiviral, anticancer, and anti-inflammatory activity and inhibits food allergies. Previous studies have
reported that inotodiol also has antiallergic effects. However, whether inotodiol inhibits hydrogen peroxide (H2O2)-
induced oxidative stress in human skin is not known. Stimulation of human dermal fibroblast cells with H2O2 is
related to skin aging and upregulation of inflammation-related proteins, along with decreased expression of
mitogen-activated protein kinases (MAPKs). Inotodiol effectively decreased nuclear factor kappa-light-chain-
enhancer of activated B cells (NF-κB), as well as nitric oxide (NO), reactive oxygen species (ROS), cyclooxygenase-2
(COX-2), and cytokines such as IL-1β and TNF-α. Moreover, inotodiol inhibited the expression of extracellular-signal-
regulated kinases 1 and 2 (ERK1/2), which are components of the MAPK signaling pathway. Furthermore, inotodiol
also suppressed NOX5 expression. Based on our results, inotodiol protects human dermal fibroblast by preventing
ERK1/2, NF-κB and NOX5 activation and attenuates the expression of inflammation genes. Inotodiol may therefore
be considered a potential candidate for developing natural antiaging products, which protects human skin from
ROS-induced injury by inhibiting the ERK1/2 and NOX5 signaling pathway.

